Effect of neonatal endotoxemia on the pancreas of adult rats.
Bacterial endotoxin (lipopolysaccharide, LPS), is the component of the cellular wall of Gram negative bacteria. Endotoxemia (sepsis) could produce multiorgan failure and could be particularly danger in the early period of life. The effects of endotoxemia induced in the neonatal period of life on the pancreatic secretory function and on pancreatic defense of adult organism have not been investigated yet. To induce endotoxemia suckling rats (30 g) have been injected intraperitoneally with LPS from E. coli (5, 10 or 15 mg/kg-day) during 5 consecutive days. Three months later in these animals (300 g) the studies on pancreatic secretion and acute pancreatitis were carried out. In the adult rats, which have been subjected in infancy to endotoxemia, basal pancreatic secretion was unaffected, whereas amylase secretions stimulated by caerulein or by diversion of pancreatic-biliary juice to the exterior were significantly, and dose-dependently reduced as compared to the untreated control. In the rats pretreated with LPS in the suckling period of life caerulein-induced amylase release from isolated pancreatic acini was significantly decreased, and dose-dependent reduction of mRNA signal for CCK1 receptor on pancreatic acini have been observed. Caerulein infusion (25 microg/kg) produced caerulein induced pancreatitis (AP) in all animals tested, that was confirmed by histological examination. In the rats, which have been subjected in the neonatal period of life to LPS (10 or 15 mg/kg-day x 5 days) all manifestations of AP have been reduced. In these animals acute inflammatory changes of pancreatic tissue have been significantly diminished. Pancreatic weight and plasma lipase activity, have been markedly decreased in these animals as compared to the control rats, subjected in the infancy to saline injection instead of LPS. Caerulein-induced fall in an antioxidative enzyme; SOD concentration was reversed and accompanied by significant reduction of lipid peroxidation products; MDA+ 4 HNE in the pancreatic tissue.


CONCLUSIONS
1/ neonatal endotoxemia reduces gene expression for CCK1 receptor and could produce impairment of the exocrine pancreatic function at adult age; 2/ Prolonged exposition of suckling rats to bacterial endotoxin attenuated acute pancreatitis induced in these animals at adult age and this effect could be related to the increased concentration of antioxidative enzyme SOD in the pancreatic tissue.
Jaworek
J
J
Department of Medical Physiology Faculty of Health Sciences, Jagiellonian University School of Medicine, Krakow, Poland. mpjawore@cyf-kr.edu.pl
Leja-Szpak
A
A
Nawrot-Porabka
K
K
Bonior
J
J
Szklarczyk
J
J
Kot
M
M
Konturek
S J
SJ
Tomaszewska
R
R
Pawlik
W W
WW
D000199:Actins / Q000378:metabolism; D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D002108:Ceruletide; D016207:Cytokines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000139:chemically induced / Q000201:enzymology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides; D010179:Pancreas / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D043886:Receptor, Cholecystokinin A / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000199:Actins; D016207:Cytokines; D006360:Heat-Shock Proteins; D008070:Lipopolysaccharides; D043886:Receptor, Cholecystokinin A; D002108:Ceruletide; D013482:Superoxide Dismutase; D008049:Lipase; D000681:Amylases